
Neuropathic Pain
Neuropathic Pain (NP) is one of the most difficult types of pain to treat in humans. NP is defined by the IASP as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”. It results from damage and sensitization of the neurons in the peripheral and central nervous systems and is characterized by long-lasting exaggerated pain behavior such as hyperalgesia and allodynia.
The majority of the preclinical models are based on a discrete peripheral nerve injury and can be related to the post-traumatic / postsurgical neuropathic pain experienced by patients.
Transpharmation offers traumatic nerve injury models that have proven their usefulness in the experimental study of NP in rodents. In these various models, the sciatic nerve is ligated or nerves emanating from the sciatic nerve (tibial and common peroneal nerves) are severed. These procedures share the common feature that the innervation of the foot remains partially intact, allowing tests for allodynia and hyperalgesia to be undertaken.
Models
Chronic Constriction Injury is a discrete peripheral nerve injury model, originally described by Bennett and Xie (1988), that closely relates to post-traumatic or postsurgical neuropathic pain in patients. Loose ligation of the sciatic nerve with chromic gut sutures induces local inflammation and intraneural constriction, producing a unilateral peripheral mononeuropathy. This results in robust mechanical and cold allodynia, tactile allodynia, and thermal hyperalgesia, with the pain phenotype persisting for at least 28 days. The model is pharmacologically validated by its responsiveness to clinically relevant neuropathic pain treatments — including pregabalin, duloxetine, naproxen, and morphine — making it a robust and widely used tool for characterizing analgesic candidates targeting peripheral neuropathic pain.
Read the full description: Chronic constriction injury (CCI)
Spared Nerve Injury, first described by Decosterd and Woolf (2000), is a model of peripheral mononeuropathy that can be related to post-traumatic or postsurgical neuropathic pain experienced by patients. It involves ligation and transection of the tibial and common peroneal branches of the sciatic nerve, while the sural nerve is deliberately spared. Mechanical hyperalgesia, mechanical allodynia, and tactile allodynia are typically assessed from Day 3 (rats) and Day 7 (mice) post-surgery to reveal the analgesic potency of test compounds.
Trigeminal neuralgia is among the most severe forms of NP, characterized by sudden, shock-like pain along the trigeminal nerve (most often the infraorbital branch). It can result from vascular compression, demyelination, or nerve trauma, closely paralleling injury mechanisms modeled preclinically. Transpharmation offers a chronic constriction injury of the infraorbital nerve (ION-CCI) model, reproducing orofacial mechanical/thermal hypersensitivity for robust translational assessment of trigeminal-mediated pain.
Type 1 diabetes is induced in rats via a single intraperitoneal injection of STZ, a toxin which selectively ablates pancreatic insulin-producing β-cells. By Day 7, animals present with significant hyperglycemia, weight loss, polydipsia, and polyuria; by Day 14, they exhibit mechanical and thermal allodynia, quantified using both von Frey and cold plate tests. The resulting painful neuropathy is alleviated by pregabalin treatment, supporting the model’s pharmacological validity for evaluating novel analgesic candidates against a major, underserved clinical indication.
In chemotherapy, cumulative dose-limiting toxicity is a major problem due to the painful neuropathy induced by antineoplastic agents. Paclitaxel-induced chronic peripheral sensory neuropathy is modeled via repeated intraperitoneal injections (2 mg/kg x4), with mechanical and cold allodynia. Oxaliplatin-induced neuropathy is generated by a single intraperitoneal injection (10 mg/kg) in both mice and rats and produces mechanical allodynia of similar duration. Both models persist for at least 2–3 weeks and are reversed by pregabalin, supporting their use for evaluating analgesic candidates against dose-limiting CIPN.
Read the full description: Chemotherapy-induced neuropathy (Oxaliplatin/Paclitaxel)
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Humanized Models PXB humanized-liver mice
SPIDAR Rapid analgesic screening
Transgenics Genetically modified mice
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